Q91WG5 · AAKG2_MOUSE
- Protein5'-AMP-activated protein kinase subunit gamma-2
- GenePrkag2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids566 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 299 | ADP 2 (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 299 | AMP 2 (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 299 | ATP 1 (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 299 | ATP 2 (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 314-319 | ADP 1 (UniProtKB | ChEBI) | ||||
Sequence: MLTITD | ||||||
Binding site | 314-319 | AMP 1 (UniProtKB | ChEBI) | ||||
Sequence: MLTITD | ||||||
Binding site | 314-319 | ATP 1 (UniProtKB | ChEBI) | ||||
Sequence: MLTITD | ||||||
Binding site | 359 | ADP 1 (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 359 | AMP 1 (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 359 | ATP 1 (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 380 | AMP 3 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 380-381 | ADP 1 (UniProtKB | ChEBI) | ||||
Sequence: HR | ||||||
Binding site | 380-381 | AMP 1 (UniProtKB | ChEBI) | ||||
Sequence: HR | ||||||
Binding site | 380-381 | ATP 1 (UniProtKB | ChEBI) | ||||
Sequence: HR | ||||||
Binding site | 381 | ATP 2 (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 399 | ADP 2 (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 399 | AMP 2 (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 399 | ATP 2 (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 429 | AMP 3 (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 434 | AMP 3 (UniProtKB | ChEBI) | ||||
Sequence: A | ||||||
Binding site | 455-456 | AMP 3 (UniProtKB | ChEBI) | ||||
Sequence: SA | ||||||
Binding site | 471-474 | ADP 2 (UniProtKB | ChEBI) | ||||
Sequence: SKFD | ||||||
Binding site | 471-474 | AMP 2 (UniProtKB | ChEBI) | ||||
Sequence: SKFD | ||||||
Binding site | 471-474 | ATP 2 (UniProtKB | ChEBI) | ||||
Sequence: SKFD | ||||||
Binding site | 498 | ADP 2 (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 498 | AMP 2 (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 498 | ATP 2 (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 527 | AMP 3 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 527-528 | ADP 2 (UniProtKB | ChEBI) | ||||
Sequence: HR | ||||||
Binding site | 527-528 | AMP 2 (UniProtKB | ChEBI) | ||||
Sequence: HR | ||||||
Binding site | 527-528 | ATP 2 (UniProtKB | ChEBI) | ||||
Sequence: HR | ||||||
Binding site | 543-546 | AMP 3 (UniProtKB | ChEBI) | ||||
Sequence: SLSD |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleotide-activated protein kinase complex | |
Cellular Component | nucleus | |
Molecular Function | ADP binding | |
Molecular Function | AMP binding | |
Molecular Function | AMP-activated protein kinase activity | |
Molecular Function | ATP binding | |
Molecular Function | cAMP-dependent protein kinase inhibitor activity | |
Molecular Function | phosphorylase kinase regulator activity | |
Molecular Function | protein kinase activator activity | |
Molecular Function | protein kinase binding | |
Molecular Function | protein kinase regulator activity | |
Biological Process | cellular response to nutrient levels | |
Biological Process | fatty acid biosynthetic process | |
Biological Process | glycogen metabolic process | |
Biological Process | intracellular signal transduction | |
Biological Process | positive regulation of peptidyl-threonine phosphorylation | |
Biological Process | regulation of fatty acid metabolic process | |
Biological Process | regulation of glycolytic process |
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended name5'-AMP-activated protein kinase subunit gamma-2
- Short namesAMPK gamma2; AMPK subunit gamma-2
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ91WG5
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Phenotypes & Variants
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 13 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000204382 | 1-566 | 5'-AMP-activated protein kinase subunit gamma-2 | |||
Sequence: MGSAAMDTKKKKEVSSPGGSSGKKNPSLKRRSLRVHIPDLSSFAMPLLDGDVENSEKHSSRKVDSPFSSGSPSRGLFSRGPQPRPSSPVSAPVRPKTSPGSPKTVFPFSYQESPPRSPRRMSFSGIFRSSSKESSPNSNPSTSPGGIRFFSRSRKTSSVSSSPSTPTQVTKQHPFPLESYKQEPERPESRIYASSSPPDTGQRFCLAFQSPARPPLASPTYHAPLRTAVLAAAPGPAEAGMLEKLEFQEEEDSESGVYMRFMRSHKCYDIVPTSSKLVVFDTTLQVKKAFFALVANGVRAAPLWESKKQSFVGMLTITDFINILHRYYKSPMVQIYELEEHKIETWRELYLQETFKPLVNISPDASLFDAVYSLIKNKIHRLPVIDPISGNALYILTHKRILKFLQLFMSDMPKPAFMKQNLDELGIGTYHNIAFIHPDTPIIKALNIFVERRISALPVVDESGKVVDIYSKFDVINLAAEKTYNNLDITVTQALQHRSQYFEGVVKCSKLETLETIVDRIVRAEVHRLVVVNEADSIVGIISLSDILQALILTPAGAKQKETETE | ||||||
Modified residue | 65 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 71 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 73 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 90 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 138 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 143 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 158 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 161 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 162 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 165 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 196 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK.
Glycosylated; O-GlcNAcylated by OGT, promoting the AMP-activated protein kinase (AMPK) activity.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Gene expression databases
Interaction
Subunit
AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2 (By similarity).
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for compositional bias, region, domain, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-17 | Basic and acidic residues | ||||
Sequence: MGSAAMDTKKKKEVSSP | ||||||
Region | 1-198 | Disordered | ||||
Sequence: MGSAAMDTKKKKEVSSPGGSSGKKNPSLKRRSLRVHIPDLSSFAMPLLDGDVENSEKHSSRKVDSPFSSGSPSRGLFSRGPQPRPSSPVSAPVRPKTSPGSPKTVFPFSYQESPPRSPRRMSFSGIFRSSSKESSPNSNPSTSPGGIRFFSRSRKTSSVSSSPSTPTQVTKQHPFPLESYKQEPERPESRIYASSSPP | ||||||
Compositional bias | 102-175 | Polar residues | ||||
Sequence: PKTVFPFSYQESPPRSPRRMSFSGIFRSSSKESSPNSNPSTSPGGIRFFSRSRKTSSVSSSPSTPTQVTKQHPF | ||||||
Domain | 272-332 | CBS 1 | ||||
Sequence: PTSSKLVVFDTTLQVKKAFFALVANGVRAAPLWESKKQSFVGMLTITDFINILHRYYKSPM | ||||||
Domain | 354-412 | CBS 2 | ||||
Sequence: TFKPLVNISPDASLFDAVYSLIKNKIHRLPVIDPISGNALYILTHKRILKFLQLFMSDM | ||||||
Motif | 367-388 | AMPK pseudosubstrate | ||||
Sequence: LFDAVYSLIKNKIHRLPVIDPI | ||||||
Domain | 427-489 | CBS 3 | ||||
Sequence: IGTYHNIAFIHPDTPIIKALNIFVERRISALPVVDESGKVVDIYSKFDVINLAAEKTYNNLDI | ||||||
Domain | 501-559 | CBS 4 | ||||
Sequence: YFEGVVKCSKLETLETIVDRIVRAEVHRLVVVNEADSIVGIISLSDILQALILTPAGAK |
Domain
The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1 (By similarity).
The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2'- and 3'-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.
Sequence similarities
Belongs to the 5'-AMP-activated protein kinase gamma subunit family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q91WG5-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- NameA
- Length566
- Mass (Da)62,949
- Last updated2011-07-27 v2
- ChecksumD112BFD69D1C5ACB
Q91WG5-2
- NameB
- Differences from canonical
- 1-240: Missing
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Features
Showing features for compositional bias, alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-17 | Basic and acidic residues | ||||
Sequence: MGSAAMDTKKKKEVSSP | ||||||
Alternative sequence | VSP_015586 | 1-240 | in isoform B | |||
Sequence: Missing | ||||||
Compositional bias | 102-175 | Polar residues | ||||
Sequence: PKTVFPFSYQESPPRSPRRMSFSGIFRSSSKESSPNSNPSTSPGGIRFFSRSRKTSSVSSSPSTPTQVTKQHPF | ||||||
Sequence conflict | 257 | in Ref. 3; AAH15283 | ||||
Sequence: V → F | ||||||
Sequence conflict | 516 | in Ref. 1; AAQ55224 | ||||
Sequence: T → N |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY348864 EMBL· GenBank· DDBJ | AAQ55224.1 EMBL· GenBank· DDBJ | mRNA | ||
AC116151 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC125270 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC015283 EMBL· GenBank· DDBJ | AAH15283.1 EMBL· GenBank· DDBJ | mRNA |